Publication: A single-cell atlas of large B cell lymphomas reveals distinct malignant archetypes predictive of clinical outcomes.

Published in: Blood 2026 Sep; ():

Authors: Baaklini S, Sarrabay A, Barthelemy C, Dahbi L, Gil L, Mossadegh-Keller N, Seth S, Hasan R, Stokes ME, Navarro JM, Huber C, Fenouil R, Escaliere B, Trombetta R, Pujol M, Dreval K, Hilton LK, Li X, Green MR, Gaulard P, Riviere B, Cuillière-Dartigues P, Llamas Gutierrez F, Pangault C, Jardin F, Lemonnier F, Brisou G, Gravelle P, Laurent C, Ortiz Estevez M, Wenzl K, Haioun C, Morin RD, Spinelli L, Huang CC, Kaplan MI, Gandhi AK, Nadel B, Roulland S, Milpied P

Summary

Large B cell lymphomas (LBCLs) exhibit significant heterogeneity which leads to disparate treatment response, with up to 40% of patients developing refractory disease or relapsing within the first two years. To understand the cellular and molecular basis of this heterogeneity, we performed single-cell RNA-seq, BCR-seq, and TCR-seq on LBCL tumor biopsies, generating an atlas of 63 LBCL cases, mostly classified as diffuse LBCL, not otherwise specified (DLBCL NOS). We identified five conserved transcriptional archetypes of malignant B cells that co-occur within individual tumors, with varying proportions across patients. Notably, high abundance of Archetype 4, characterized by memory B cell features and quiescence markers, correlated with poor event-free survival following standard immunochemotherapy, a finding which was validated in independent cohorts through deconvolution of bulk RNA-seq data. Our study provides a novel framework for patient stratification based on the quantification of malignant cellular states, with implications for precision therapy of LBCLs.

Link to Pubmed [PMID] – 42752800

Link to DOI – 10.1182/blood.2026033056